Cancer articles within Nature Communications

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  • Article
    | Open Access

    γ-H2AX The Ser139 phosphorylated form of H2AX, γ-H2AX, is generated in response to DNA double-strand breaks and is involved in the repair process. Here, Sone et al.show that H2AX K134 methylation by SUV39H2 is crucial for the production of γ-H2AX, and that loss of methylation correlates with radio- and chemosensitivity.

    • Kenbun Sone
    • , Lianhua Piao
    •  & Ryuji Hamamoto

  • Article |

    Cancer cells often develop resistance to radiotherapy but the molecular mechanisms responsible remain unclear. Here the authors show that miR-205 promotes radiosensitivity and is downregulated in radioresistant subpopulations of breast cancer cells, and that its loss is associated with poor distant relapse-free survival in breast cancer patients.

    • Peijing Zhang
    • , Li Wang
    •  & Li Ma

  • Article |

    Human cancers are characterised by increased levels of genomic instability. Here, the authors show that a new class of mutation that occurs in glioblastoma, double minutes, may facilitate tumour drug resistance by acquiring gain-of-function extrachromosomal mutations, mediated by focal amplifications.

    • Sergey Nikolaev
    • , Federico Santoni
    •  & Stylianos E. Antonarakis

  • Article |

    Despite the treatment efficacy of combining BRAF and MEK inhibitors, a third of BRAF-mutant metastatic melanoma patients treated with this therapy progress within 6 months. Here, the authors sequence tumours from patients with BRAFV600-mutant melanoma metastases and identify mutations that confer resistance to combination therapy.

    • Georgina V. Long
    • , Carina Fung
    •  & Helen Rizos

  • Article
    | Open Access

    Metastatic castration-resistant prostate cancer is treated with the microtubule-stabilizing drugs taxanes, but resistance ultimately develops. Here Galletti et al.show that ERG, a transcription factor commonly overexpressed in prostate cancers, confers taxane resistance by binding to soluble tubulin.

    • Giuseppe Galletti
    • , Alexandre Matov
    •  & David S. Rickman

  • Article
    | Open Access

    PHD3 is a hypoxia-inducible prolyl hydroxylase that regulates stability of HIF-1. Here Garvalov et al.report a hydroxylase-independent role of PHD3 in gliomas as a scaffolding protein that promotes internalization and limits signalling of EGFR upon ligand binding, thus inhibiting growth in hypoxia.

    • Boyan K. Garvalov
    • , Franziska Foss
    •  & Till Acker

  • Article |

    The small GTPase RhoA has oncogenic effects in several cancer types. Here the authors show that loss of RhoA accelerates colon cancer progression by promoting accumulation of nuclear ß-catenin, resulting in enhanced proliferation and invasion mediated by the Wnt signalling pathway in human and murine colon cancer cells.

    • Paulo Rodrigues
    • , Irati Macaya
    •  & Diego Arango

  • Article
    | Open Access

    While prostate cancer predominantly exhibits androgen dependence, oestrogen receptor (ER) signalling is also involved. Here, Chakravarty et al.show that ERα regulates the expression of the NEAT1 long non-coding RNA, which in turn promotes tumorigenesis by maintaining an oncogenic programme/cascade.

    • Dimple Chakravarty
    • , Andrea Sboner
    •  & Mark A. Rubin

  • Article |

    The pyruvate kinase type M2 (PKM2) has a well-established role in cancer due to its functions in regulating glucose metabolism, G1-S transition and mitotic checkpoint. Here the authors identified a novel role for PKM2 in regulating cytokinesis in cancer cells through the phosphorylation of the myosin light chain 2 at the contractile ring.

    • Yuhui Jiang
    • , Yugang Wang
    •  & Zhimin Lu

  • Article |

    BRMS1, a component of the Sin3A–HDAC repressor complex, blocks invasion and migration of breast cancer cells. Here the authors show that BRMS1-like (BRMS1L) inhibits breast cancer metastasis by blocking epithelial to mesenchymal transition through transcriptional suppression of the FZD10 receptor for Wnt ligands.

    • Chang Gong
    • , Shaohua Qu
    •  & Erwei Song

  • Article |

    Cancer can result from mutations in more than one gene and these multiple mutated genes are often functionally dependent on each other; this interaction is known as epistasis. Here, the authors use a combinatorial RNAi screen to identify epistatic genes that are mutated in breast cancer and reveal large numbers of previously unreported gene interactions.

    • Xiaoyue Wang
    • , Audrey Q. Fu
    •  & Kevin P. White

  • Article |

    The accumulation of genetic and epigenetic mutations in cancer cells can drive malignant growth. Here, the authors model the evolution of intratumoral diversity and examine the classification of driver and passenger mutations, heterogeneity within tumours, and the dynamics of tumour response to targeted therapies.

    • R. A. Gatenby
    • , J. J. Cunningham
    •  & J. S. Brown

  • Article
    | Open Access

    Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive and heterogeneous type of non-Hodgkin’s lymphoma. Here the authors demonstrate that the differential regulation of eIF4E1 and eIF4E3 by the MAPK-interacting kinases is involved in DLBCL aetiology through modification of the cellular translatome.

    • Ari L. Landon
    • , Parameswary A. Muniandy
    •  & Ronald B. Gartenhaus

  • Article
    | Open Access

    BRCA1 is a key breast and ovarian cancer suppressor involved in DSB repair. Here, the authors show that cells heterozygous for several BRCA1mutations are universally defective in the response to replication stress, which could contribute to the BRCA1 breast cancer development pathway.

    • Shailja Pathania
    • , Sangeeta Bade
    •  & David M. Livingston

  • Article
    | Open Access

    Response to drug therapy in colorectal cancer (CRC) patients has been associated with tumour heterogeneity. Here the authors analyse DNA copy number aberrations in primary tumours from CRC patients and identify genetic variants that influence drug response.

    • Josien C. Haan
    • , Mariette Labots
    •  & Gerrit A. Meijer

  • Article |

    The Ras family of proteins is frequently mutated in cancer, and free radical oxidants can also activate these proteins via modifications at cysteine 118 (C118). Here the authors introduce a C118S mutant Krasgene into mice and show that this mutant allele results in a reduction in lung tumorigenesis.

    • Lu Huang
    • , John Carney
    •  & Christopher M. Counter

  • Article |

    The COP9 signalosome (CSN) is a protein complex involved in protein degradation and tumorigenesis. Here the authors show that the CSN6 subunit antagonizes the deneddylation function of CSN5 towards ubiquitin ligase Cullin-1, resulting in Fbxw7 ubiquitin ligase degradation and thereby stabilization of the Fbxw7 target Myc.

    • Jian Chen
    • , Ji-Hyun Shin
    •  & Mong-Hong Lee

  • Article |

    Mutations of hCdc73, a component of the PAFc complex that regulates RNA polymerase II-dependent transcription, have been associated with parathyroid carcinoma. Here the authors show that hCdc73 regulates the mRNA stability of p53 through the interaction with eEF1Bγ, a translation elongation complex subunit, and hSki8, a component of mRNA decay complex.

    • Jay-Hyun Jo
    • , Tae-Moon Chung
    •  & Joo-Yeon Yoo

  • Article |

    Overexpression of the FOXM1 transcription factor occurs in several cancer and correlates with poor prognoses. Here, the authors identify a novel small molecule capable of displacing FOXM1 from its DNA consensus motif in vitro, displace it from target promoters and downregulate the expression of its target genes cancer cells.

    • Michael V. Gormally
    • , Thomas S. Dexheimer
    •  & Shankar Balasubramanian

  • Article |

    It is known that mesenchymal stem cells contribute to chemotherapy resistance by secreting polyunsaturated fatty acids. Here the authors show that macrophages in the spleen secrete lysophosphatidylcholines and contribute to chemotherapy resistance by altering the tumour's DNA damage response.

    • Julia M. Houthuijzen
    • , Laura G. M. Daenen
    •  & Emile E Voest

  • Article |

    Rad54B is a poorly characterized DNA damage repair protein homologous to Rad54, a protein implicated in DNA damage repair through homologous recombination. Here the authors implicate Rad54B as a modulator of the DNA damage response through its interaction with the MDM2–MDMX complex to regulate p53 degradation.

    • Takaaki Yasuhara
    • , Takahiko Suzuki
    •  & Kiyoshi Miyagawa

  • Article |

    The abundant IincRNA growth arrest-specific 5 (Gas5) inhibits the transcriptional activity of steroid hormone receptors (SRs) through direct competition for DNA binding. Here the authors use X-ray crystallography, NMR and complementary biochemical approaches to elucidate the molecular and evolutionary mechanisms that guide Gas5 binding to SRs.

    • William H. Hudson
    • , Mark R. Pickard
    •  & Eric A. Ortlund

  • Article |

    Mutations within the ARF tumour suppressor—encoded by the CDKN2A locus—have been associated with familial melanoma through an unknown mechanism. Here the authors uncover a melanoma protective function of ARF through its ability to interact with dysfunctional mitochondria and maintain low levels of cellular superoxide.

    • Claus Christensen
    • , Jirina Bartkova
    •  & Per Guldberg

  • Article |

    The Sonic hedgehog (Shh) signalling pathway plays important roles during development and its abnormal activation has been implicated in cancer. Here the authors uncover an epigenetic switch in the Shh pathway that involves the PRC2, Jmjd3/Kdm6b and Set1/MLL complexes in regulating signalling induced gene activation.

    • Xuanming Shi
    • , Zilai Zhang
    •  & Jiang Wu

  • Article
    | Open Access

    The cross-talk between constitutively active EGFR- and NF-κB-dependent pathways in cancer is poorly understood. Here, the authors identify KIAA1199 as a BCL3 and NF-κB-regulated protein that is expressed in cervical lesions and promotes tumorigenesis through Plexin A2 binding and regulation of EGFR stability.

    • Kateryna Shostak
    • , Xin Zhang
    •  & Alain Chariot

  • Article |

    The death receptor CD95/Fas induces apoptosis of many normal cells but prevents necrotic death of cancer cells. Here the authors demonstrate that CD95 activation promotes a cancer stem cell (CSC) phenotype, and that CSCs but not differentiated cancer cells are resistant to CD95-mediated apoptosis and depend on CD95 signalling to prevent necrosis.

    • Paolo Ceppi
    • , Abbas Hadji
    •  & Marcus E. Peter

  • Article
    | Open Access

    While several human papilloma virus (HPV) vaccines exist, a highly effective vaccine that mediates regression of HPV-induced tumours is lacking. Here the authors show that a therapeutic DNA vaccine-induced HPV-specific polyfunctional CD8 T cell in 7 out of 9 patients who all exhibited complete regression of lesions and viral clearance.

    • Tae Jin Kim
    • , Hyun-Tak Jin
    •  & Young Chul Sung

  • Article |

    Renal cancer accounts for 2.4% of all adult cancers and its incidence is increasing worldwide. Here, the authors carry out genome and transcriptome sequencing of clear cell renal cell carcinomas (ccRCCs) and highlight genomic aberrations and biological pathways underlying ccRCC tumorigenesis.

    • Ghislaine Scelo
    • , Yasser Riazalhosseini
    •  & G. Mark Lathrop

  • Article |

    MicroRNAs play important roles in the maintenance of cellular homeostasis through the post-transcriptional regulation of gene expression. Here, the authors implicate loss of the miRNA biogenesis factor Drosha and altered miRNA maturation in tumour progression under hypoxic conditions.

    • Rajesha Rupaimoole
    • , Sherry Y. Wu
    •  & Anil K. Sood

  • Article
    | Open Access

    Loss-of-function mutations in tumour suppressor genes are associated with oesophageal adenocarcinoma (EAC), but the mechanisms underlying EAC development remain unclear. Here, the authors show that EACs present a high frequency of genomic catastrophes resulting in amplification of potent oncogenes.

    • Katia Nones
    • , Nicola Waddell
    •  & Andrew P. Barbour

  • Article |

    Reduced expression of DICER—responsible for the processing of microRNA precursors—was previously linked to poor clinical outcomes in cancer patients. Here, the authors uncover an epigenetic mechanism by which hypoxia suppresses DICER expression and deregulates the miR-200-Zeb1 circuit in breast cancer to promote the tumour phenotype.

    • Twan van den Beucken
    • , Elizabeth Koch
    •  & Bradly G. Wouters

  • Article
    | Open Access

    Mitotic spindle assembly requires strict control of microtubule nucleation by γ-tubulin ring complexes. Olmsted et al. report that the kinesin-like proteins Pkl1 and Cut7 antagonistically regulate nucleation in fission yeast, and show that a Pkl1 peptide blocks spindle assembly in human cancer cells.

    • Zachary T. Olmsted
    • , Andrew G. Colliver
    •  & Janet L. Paluh

  • Article |

    Simultaneous mitochondrial dysfunction and Ras activation, which is commonly observed in cancer cells, has been shown to trigger the proliferation of neighbouring tissues in Drosophila. Nakamura et al.reveal that this effect is driven by a DNA-damage-induced senescence-associated secretory phenotype.

    • Mai Nakamura
    • , Shizue Ohsawa
    •  & Tatsushi Igaki

  • Article |

    Tumours acquire new vasculature through angiogenesis or through alternative pathways including the less understood vasculogenesis mimicry. Here the authors identify a vasculogenic mimicry-competent subpopulation of melanoma cells that expresses the vascular cell adhesion molecule PECAM1, but not VEGFR-2.

    • James M. Dunleavey
    • , Lin Xiao
    •  & Andrew C. Dudley

  • Article
    | Open Access

    A subset of cancers maintains telomere length independently of telomerase by activating alternative lengthening of telomeres (ALT) pathways. Here the authors show that RNaseH1 modulates telomeric homologous recombination frequencies in ALT cells by regulating the levels of RNA–DNA hybrids between TERRA and telomeric DNA.

    • Rajika Arora
    • , Yongwoo Lee
    •  & Claus M. Azzalin

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